In this grant application, we propose to develop and optimize two new fluorine-18 (18F) reactions for the synthesis of 18F-labeled small molecules as useful, generally available tools for positron emission tomography (PET). Our goal is to provide readily available reagents that can be used by the entire radiochemistry community for the robust and simple synthesis of 18F-fluorinated probes from readily available materials. Our preliminary data suggest that the proposed reactions combine the simplicity of conventional fluorination chemistry with the large substrate scope of modern late-stage fluorination reactions. Our approach is enabled by novel chemical reactivity that can convert available materials directly into the corresponding fluorinated analogs. Positron emission tomography (PET) is a non-invasive, high sensitivity imaging technology that can be used to diagnose and study human diseases. PET can provide information about normal or aberrant human physiology and is a powerful tool for monitoring disease progression and treatment response. Over the past decade, PET imaging has had an impact in studying several diseases, such as cancer and neurological diseases, and is also beginning to expedite the development of new pharmaceuticals. However, the vast majority of molecules (even those that contain fluorine) cannot currently be labeled with the positron-emitting 18F isotope necessary for imaging. A clear need exists for more versatile and robust radiochemistry methods for incorporation of the 18F isotope. Our lab has invented a new reagent and a new reaction to incorporate the positron-emitting nuclide 18F into molecules based on new chemical reactivity. We have already demonstrated that we can provide aryl and alkyl fluorides from readily available phenols and alcohols, respectively. We propose here reaction development to furnish practical, readily performed methods for the synthesis of PET probes. Reaction optimization will be guided by a mechanism-based approach. We will showcase the utility and generality of our new methods by preparing eight radiotracers that are challenging to prepare with conventional methods.